Local anesthetic articaine ameliorates LPS-induced acute kidney injury via inhibition of NF-ĸB activation and the NLRP3 inflammasome pathway

J Biochem Mol Toxicol. 2020 Oct;34(10):e22554. doi: 10.1002/jbt.22554. Epub 2020 Jul 20.

Abstract

The present study was conducted to determine the protective effect of articaine (ART) in an lipopolysaccharide (LPS)-induced acute kidney injury (AKI) animal model. The results suggest ART causes a significant decrease in serum blood urea nitrogen, creatinine, and serum cystatin C level, showing a protective effect against LPS-induced AKI. This has been further supported by histopathological findings of kidney tissues. The level of tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in serum and kidney tissues was remarkably inhibited by ART in a dose-dependent manner. ART causes a significant reduction of malondialdehyde and increases the activities of glutathione and superoxide dismutase with an increase in dose as compared to the LPS-treated group. Moreover, the ART-treated group showed dose-dependent inhibition of LPS-induced nuclear factor-κB activation and TLR4 expression as confirmed by Western blot analysis. The level of Bcl-2 family genes (Bcl-2 and Bax) was restored near to normal by ART. Collectively, all the above results indicated that ART had protective effects against LPS-induced AKI by blocking inflammatory and oxidative responses.

Keywords: LPS; NF-κB; acute kidney injury; inflammation; oxidative stress.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Anesthetics, Local / administration & dosage
  • Anesthetics, Local / pharmacology*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers / blood
  • Blood Urea Nitrogen
  • Carticaine / administration & dosage
  • Carticaine / pharmacology*
  • Creatinine / blood
  • Cystatin C / blood
  • Cytokines / blood
  • Dose-Response Relationship, Drug
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Inflammation Mediators / blood
  • Kidney / pathology
  • Lipopolysaccharides / toxicity*
  • Male
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Toll-Like Receptor 4 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Anesthetics, Local
  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Cystatin C
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Nlrp2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Creatinine
  • Carticaine